SAN ANTONIO – Proton pump inhibitor use was associated with an 80% increase in the risk of Clostridium difficile–associated diarrhea, based on data from a meta-analysis of 21 studies.

Proton pump inhibitors (such as Prilosec or Prevacid) are generally considered safe, resulting in some degree of indiscriminate use, said Dr. Sailajah Janarthanan of Wayne State University in Detroit. PPIs have faced scrutiny for a possible association with C. difficile–associated diarrhea (CDAD), but results from previous studies have yielded mixed results, Dr. Janarthanan said.increase in the risk of Clostridium difficile–associated diarrhea, an analysis indicates.

"Given the millions of individuals on PPIs, even a slight increase in the risk of CDAD conferred by these drugs will have major public health implications," she emphasized.

To explore the relationship between PPIs and CDAD, Dr. Janarthanan and her colleagues looked at data from 21 peer-reviewed published studies. The 7 cohort studies and 14 case-control studies included 133,054 individuals.

Overall, there was a significant increase in the risk of CDAD in patients taking PPIs (risk estimate, 1.80). The risk estimate in the case-control studies was 1.55 and in the cohort studies 2.07. The CDAD risk was significantly higher for patients taking PPIs whether the types of studies were considered separately or as a whole.

C. difficile represents an escalating threat to public health, and CDAD cost the United States an estimated $3 billion in 2005, Dr. Janarthanan said at the annual meeting of the American College of Gastroenterology.

The results of the studies reviewed by Dr. Janarthanan and her associates were limited by the lack of randomized, controlled trials, she noted, and the impact of PPIs on CDAD remains controversial.

"Indiscriminate use of PPIs without proper indication should be discouraged," she said. "There is a real-time need for guidelines on the use of PPIs, especially in hospitals."